Based on evidence that an infectious agent or agents may play a role in the etiology of some schizophrenic illnesses, we are culturing fresh CSF from patients with schizophrenia and from control subjects on human neuroblastoma cells. Our previous studies have included immunocytochemical investigations for antigens to cytomegalvirus (CMV), herpes simplex virus (HSV), varicella virus, rubella and mumps. Although sporadic cases have shown positive results with immunocytochemical studies, these have been inconsistent are rare. We have also undertaken in situ hybridization probes for CMV, and cultivation of schizophrenic and control brain specimens on cultures of human and non-human neural tissue without success. Using special stains for glia we have evaluated the brains of guinea pigs and primates previously inoculated with schizophrenic and control brain tissue. During the past year we have investigated the effects of cerebrospinal fluid and sterile brain tissue from schizophrenic patients on the growth, peptide production and morphology of cultured human neuroblastoma cells. One line of human neuroblastoma cells (SHEP) has shown a consistent change in growth with loss of contact inhibition and piling up of cells to higher confluence commencing several months after incubation with schizophrenic CSF in 6 out of 7 cases, but in no control inoculated cells. Adenylcylase production is increased in schizophrenic CSF treated cells and the effect on cell growth has been passaged with cell free media. Two dimensional electrophoresis gels demonstrate differences in protein in schizophrenic compared with control gels. Further studies in progress with these transformed cells include electron microscopic examination (Dr. Peggy Swoveland), studies for reverse transcriptase (negative), ELISA and immunocytochemical studies following application of control and schizophrenic sera to search for antibodies (negative so far).